One goal of regenerative medicine is to be able to convert adult cells into other cell types for tissue repair and regeneration. Cells of adult organisms arise from sequential differentiation steps that are generally thought to be irreversible1. Biologists often describe this process of development as proceeding from an undifferentiated (embryonic) cell to a terminally differentiated cell that forms part of an adult tissue or organ. There are rare examples, however, in which cells of one type can be converted to another type in a process called cellular reprogramming or lineage reprogramming (Hochedlinger et al., Nature, 2006, 441, 1061-1067; Orkin S et al., Cell, 2008; 132; 631-644). Various forms of cellular reprogramming are referred to in the literature as transdifferentiation, dedifferentiation, or transdetermination2. For example, cellular reprogramming has been reported in amphibian limb regeneration and fly imaginal disc identity switches3,4, and it may be central to certain types of pathological metaplasia2. There is long standing interest and fascination in reprogramming studies, in part because of the promise of harnessing this phenomenon for regenerative medicine whereby abundant adult cells that can be easily harvested would be converted to other medically important cell types to repair diseased or damaged tissues.
Somatic cell nuclear transfer (SCNT), developed in the 1960s, demonstrated that nuclei from differentiated adult cells could be reprogrammed to a totipotent state following injection into enucleated eggs5,6. More recently, it was shown that a small number of transcription factors can reprogram cultured adult skin cells to pluripotent stem cells7-12. These studies point to the possibility of regenerating mammalian tissues by first reverting skin or other adult cells to pluripotent stem cells and then redifferentiating these into various cell types.